3-(Trifluoromethyl)pyridine-2-carbonitrile → 1-[3-(Trifluoromethyl)pyridin-2-yl]ethan-1-one

HRID 1724830Notes

Reaction equation

HRID 1724830 reaction equation
C(C1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][N:4]=1)#N.[CH3:13][Mg]I.CC[O:18][CH2:19][CH3:20]>C1COCC1>[C:19]([C:20]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][N:4]=1)(=[O:18])[CH3:13]

Participants

4

Reactant 2

HCID 223215743-(Trifluoromethyl)pyridine-2-carbonitrileHCID 178467823HCID 178467823, compound

Product 1

HCID 534031371-[3-(Trifluoromethyl)pyridin-2-yl]ethan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-cyano-3-trifluoromethylpyridine (179 g; 1.04 mol) and THF (1200 mL) are combined in a 5.0 liter flask and cooled with and ice and salt mixture. 3.0 M MeMgI/Et2O (694 mL) is added drop wise over a period of 90 minutes while maintaining the inside temperature of the reaction mixture below 5° C. After the addition, the reaction mixture is stirred at 0° C. for another 30 minutes, and is then slowly poured over 3.0 kg of crushed ice in a 12 liter vessel with stirring (6° C.). The undissolved magnesium salts from the original reaction vessel are quenched with ice (750 g) and transferred to the 12 liter vessel. The resulting mixture is acidified with 6.0 N aq. HCl to pH 2.0 and stirred for 30 minutes at <10° C. The mixture is then extracted with EtOAc (5×1 liters), and the combined extracts are washed with brine (1.5 liters) and dried with Na2SO4 (500 g). The dried extract is filtered and concentrated in vacuum at 40° C. to afford a dark brown oil. The crude product is distilled under vacuum to give 2-acetyl-3-trifluoromethylpyridine as a clear pale yellow liquid.

Workup

  1. temperaturecooled with and ice and salt mixture
  2. temperaturewhile maintaining the inside temperature of the reaction mixture below 5° C
  3. additionAfter the addition
  4. stirringwith stirring (6° C.)
  5. customThe undissolved magnesium salts from the original reaction vessel are quenched with ice (750 g)
  6. stirringstirred for 30 minutes at <10° C
  7. extractionThe mixture is then extracted with EtOAc (5×1 liters)
  8. washthe combined extracts are washed with brine (1.5 liters)
  9. dry with materialdried with Na2SO4 (500 g)
  10. extractionThe dried extract
  11. filtrationis filtered
  12. concentrationconcentrated in vacuum at 40° C.
  13. customto afford a dark brown oil
  14. distillationThe crude product is distilled under vacuum

Sources & evidence

ORD record
ord-fed2fdf491a34d6abba78fd9ff6e2a36
Source dataset
uspto-grants-2009_02
Patent number
US07488740B2

Reaction notes

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